Erythromycins A through D, represented by formula (E),
______________________________________ 1 #STR2## Erythromycin R.sup.a R.sup.b ______________________________________ A --OH --CH.sub.3 B --H --CH.sub.3 C --OH --H D --H --H ______________________________________
are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection.
Some erythromycin derivatives have use as prokinetic agents. For example, an erythromycin B derivative, having the formula: ##STR3## has been described as a prokinetic agent having use in the treatment of gastrointestinal motility disorders (see P. A. Lartey et al., J. Med. Chem., 38 (1793-1798 (1995); and R. Faghih, et al., PCT application WO 9313780, published Jul. 22, 1993).
The preparation of these prokinetic compounds requires the preparation of the intermediate compounds, N-demethyl-4"-deoxy-erythromycin A and N-demethyl-4"-deoxy-erythromycin B. More efficient methods of preparation of these compounds are needed to ensure more efficient synthesis and wider availability of the desired prokinetic agents.
One procedure for the preparation of N-demethyl derivatives of various macrolide antibiotics has been described in U.S. Pat. No. 3,725,385, issued Apr. 3, 1973, which teaches that the methyl group may be removed by a one-step treatment with a single addition of iodine in a pH-adjusted solution at from -10.degree. C. to 50.degree. C.